Cargando…

The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow–derive...

Descripción completa

Detalles Bibliográficos
Autores principales: Tan, Qian, Wu, Jiang‐Yan, Liu, Yao‐Xi, Liu, Kun, Tang, Jin, Ye, Wei‐Hua, Zhu, Guang‐Hui, Mei, Hai‐Bo, Yang, Ge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576311/
https://www.ncbi.nlm.nih.gov/pubmed/32862562
http://dx.doi.org/10.1111/jcmm.15767
_version_ 1783597994286776320
author Tan, Qian
Wu, Jiang‐Yan
Liu, Yao‐Xi
Liu, Kun
Tang, Jin
Ye, Wei‐Hua
Zhu, Guang‐Hui
Mei, Hai‐Bo
Yang, Ge
author_facet Tan, Qian
Wu, Jiang‐Yan
Liu, Yao‐Xi
Liu, Kun
Tang, Jin
Ye, Wei‐Hua
Zhu, Guang‐Hui
Mei, Hai‐Bo
Yang, Ge
author_sort Tan, Qian
collection PubMed
description Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non‐union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT‐PCR, Western blot and immunostaining assays. Finally, we injected lentivirus‐NF1 (Lv‐NF1) to rat non‐union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down‐regulated in non‐union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non‐union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non‐union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.
format Online
Article
Text
id pubmed-7576311
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-75763112020-10-23 The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture Tan, Qian Wu, Jiang‐Yan Liu, Yao‐Xi Liu, Kun Tang, Jin Ye, Wei‐Hua Zhu, Guang‐Hui Mei, Hai‐Bo Yang, Ge J Cell Mol Med Original Articles Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non‐union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT‐PCR, Western blot and immunostaining assays. Finally, we injected lentivirus‐NF1 (Lv‐NF1) to rat non‐union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down‐regulated in non‐union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non‐union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non‐union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing. John Wiley and Sons Inc. 2020-08-30 2020-10 /pmc/articles/PMC7576311/ /pubmed/32862562 http://dx.doi.org/10.1111/jcmm.15767 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tan, Qian
Wu, Jiang‐Yan
Liu, Yao‐Xi
Liu, Kun
Tang, Jin
Ye, Wei‐Hua
Zhu, Guang‐Hui
Mei, Hai‐Bo
Yang, Ge
The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title_full The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title_fullStr The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title_full_unstemmed The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title_short The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture
title_sort neurofibromatosis type i gene promotes autophagy via mtorc1 signalling pathway to enhance new bone formation after fracture
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576311/
https://www.ncbi.nlm.nih.gov/pubmed/32862562
http://dx.doi.org/10.1111/jcmm.15767
work_keys_str_mv AT tanqian theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT wujiangyan theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT liuyaoxi theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT liukun theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT tangjin theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT yeweihua theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT zhuguanghui theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT meihaibo theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT yangge theneurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT tanqian neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT wujiangyan neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT liuyaoxi neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT liukun neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT tangjin neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT yeweihua neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT zhuguanghui neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT meihaibo neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture
AT yangge neurofibromatosistypeigenepromotesautophagyviamtorc1signallingpathwaytoenhancenewboneformationafterfracture